Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called “human-on-a-chip” ...

The Multi-Organ-Chip platform is a microphysiological system developed to evaluate toxicity and efficacy of drugs, and adverse effects of cosmetics, chemicals and alike in a sub-systemic mode. At the scale of a microscope glass slide, it comprises several compartments for the co-cultivation of human 3D tissue constructs. The organoids are physically separated, yet, interconnected through perfus...

Regulatory T cells (Tregs) are essential mediators of tolerance and crucial for the containment of inflammatory immune reactions. Their immunosuppressive potential is currently investigated for the treatment of inflammatory diseases. However, conversion between the Treg and conventional T cell (Tcon) compartment has been described, comprising the induction or loss of the regulatory phenotype in...

Systemic lupus erythematosus (SLE) is a chronic and systemic autoimmune disorder characterized by loss of immune tolerance towards nuclear antigens such as SmD1, RNP70, Histone, Ro, and La. Besides the production of autoantibodies that directed to nuclear antigens, CD4+ T cells with T cell receptor specific to nuclear antigens may also trigger autoimmune responses leading to severe organ inflam...

The advantage of cell based assays used as biosensors is the direct access to hardly obtainable parameters like toxicity, mutagenicity and pharmacological effectiveness. Within the last few years we established a micro fluidic platform including a peristaltic micro pump as well as several valves, manifolds and micro channels [1]. For optical online monitoring the micro fluidic system is bonded ...

For in vitro drug screening a modified perfusion micro-bioreactor system with integrated hollow fibres will be demonstrated. This biocompatible system consists of an integrated closed flow circuit that includes reservoirs and pneumatic micro pumps. Additional optical online-monitoring devices allow the observation during the cell cultivation. The embedded hollow fibre system which acts as cell ...

Flow rate and wall shear stress are important parameters for perfused cell culture systems and should be monitored. An easy and non-invasive method is the particle image velocimetry (PIV). In this work PIV was used to characterize a cell culture system with included peristaltic pump. The time-dependent flow profile was measured on several points of the chip for different pumping speeds to figur...

Systemic absorption and metabolism of drugs in the small intestine, metabolism by the liver as well as excretion by the kidney are key determinants of efficacy and safety for therapeutic candidates. However, these systemic responses of applied substances lack in most in vitro assays. In this study, a microphysiological system maintaining the functionality of four organs over 28 days in co-cultu...

While skeletal muscles can recover from minor injuries, severe trauma can often induce irreversible structural damage such as extensive scar tissue formation and damaged muscle fibers. This leads to functional deficits and loss in the quality of life of patients. Effective treatment of severe muscle injuries is currently an unmet clinical need. In such cases, a therapeutic intervention such as ...

Liver transplantation is currently the only successful treatment to cure acute or acute-on-chronic liver failure. However, the number of patients waiting for a donor organ is constantly rising due to scarcity of organ donations. To overcome this bottleneck different bio-artificial liver technologies are under investigation, which may take over functions of the diseased liver until a suitable do...

Skin wound infections are a significant and increasing health problem, and antibiotic resistance
is increasing. Mast cells have been shown to contribute to host defence responses in bacterial
infections. Their role in skin wound infection is presently unknown. We subjected several mast
cell-deficient mouse strains to Pseudomonas aeruginosa skin wound infection and found
significantly delaye...

A new simple method for non-invasive cell culture viability monitoring based on vital fluorescent stains is introduced, and its efficiency for long-term experiments on cells is demonstrated. In contrast to common methods for cell viability control, which are usually either destructive (like flow-type counters or dead cells coloring and counting), or hardly quantitative like fluorescent microsco...

A chip-based system mimicking the transport function of the human cardiovascular system has been established at minute but standardized microsystem scale. A peristaltic on-chip micropump generates pulsatile shear stress in a widely adjustable physiological range within a microchannel circuit entirely covered on all fluid contact surfaces with human dermal microvascular endothelial cells. This m...